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Lyu Y, Verma VK, Lee Y, et al. Remodeling of t-system and proteins underlying excitation-contraction coupling in aging versus failing human heart. NPJ Aging Mech Dis. 2021;7(1):16doi: 10.1038/s41514-021-00066-7.
Lyu, Y., Verma, V. K., Lee, Y., Taleb, I., Badolia, R., Shankar, T. S., Kyriakopoulos, C. P., Selzman, C. H., Caine, W., Alharethi, R., Navankasattusas, S., Seidel, T., Drakos, S. G., & Sachse, F. B. (2021). Remodeling of t-system and proteins underlying excitation-contraction coupling in aging versus failing human heart. NPJ aging and mechanisms of disease, 7(1), 16. https://doi.org/10.1038/s41514-021-00066-7
Lyu, Yankun, et al. "Remodeling of t-system and proteins underlying excitation-contraction coupling in aging versus failing human heart." NPJ aging and mechanisms of disease vol. 7,1 (2021): 16. doi: https://doi.org/10.1038/s41514-021-00066-7
Lyu Y, Verma VK, Lee Y, Taleb I, Badolia R, Shankar TS, Kyriakopoulos CP, Selzman CH, Caine W, Alharethi R, Navankasattusas S, Seidel T, Drakos SG, Sachse FB. Remodeling of t-system and proteins underlying excitation-contraction coupling in aging versus failing human heart. NPJ Aging Mech Dis. 2021 May 28;7(1):16. doi: 10.1038/s41514-021-00066-7. PMID: 34050186; PMCID: PMC8163749.
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NPJ Aging Mech Dis. 2021 May 28;7(1):16. doi: 10.1038/s41514-021-00066-7.

Remodeling of t-system and proteins underlying excitation-contraction coupling in aging versus failing human heart.

NPJ aging and mechanisms of disease

Yankun Lyu, Vipin K Verma, Younjee Lee, Iosif Taleb, Rachit Badolia, Thirupura S Shankar, Christos P Kyriakopoulos, Craig H Selzman, William Caine, Rami Alharethi, Sutip Navankasattusas, Thomas Seidel, Stavros G Drakos, Frank B Sachse

Affiliations

  1. Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, USA.
  2. Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, USA.
  3. Utah Transplantation Affiliated Hospitals (U.T.A.H.) Cardiac Transplant Program, University of Utah Health & School of Medicine, Intermountain Medical Center, VA Medical Center, Salt Lake City, UT, USA.
  4. Institute of Cellular and Molecular Physiology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen-Nürnberg, Germany.
  5. Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, USA. [email protected].
  6. Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, USA. [email protected].
  7. Utah Transplantation Affiliated Hospitals (U.T.A.H.) Cardiac Transplant Program, University of Utah Health & School of Medicine, Intermountain Medical Center, VA Medical Center, Salt Lake City, UT, USA. [email protected].
  8. Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT, USA. [email protected].
  9. Department of Biomedical Engineering, University of Utah, Salt Lake City, UT, USA. [email protected].

PMID: 34050186 PMCID: PMC8163749 DOI: 10.1038/s41514-021-00066-7

Abstract

It is well established that the aging heart progressively remodels towards a senescent phenotype, but alterations of cellular microstructure and their differences to chronic heart failure (HF) associated remodeling remain ill-defined. Here, we show that the transverse tubular system (t-system) and proteins underlying excitation-contraction coupling in cardiomyocytes are characteristically remodeled with age. We shed light on mechanisms of this remodeling and identified similarities and differences to chronic HF. Using left ventricular myocardium from donors and HF patients with ages between 19 and 75 years, we established a library of 3D reconstructions of the t-system as well as ryanodine receptor (RyR) and junctophilin 2 (JPH2) clusters. Aging was characterized by t-system alterations and sarcolemmal dissociation of RyR clusters. This remodeling was less pronounced than in HF and accompanied by major alterations of JPH2 arrangement. Our study indicates that targeting sarcolemmal association of JPH2 might ameliorate age-associated deficiencies of heart function.

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